Computational Approach to the Receptor‐Bound Conformation of Cyclosporin A

The conversion of the conformation of cyclosporin A (CsA) observed in CHCl₃ to the receptor‐bound state is investigated by two molecular‐mechanics methods, template forcing and dynamic forcing. The conformations of CsA in CHCl₃ and complexed with LiCl in THF as determined by NMR are used as starting structures. The transition starting from the CsA/CHCl₃‐derived conformation is hindered by steric interactions of two side chains (MeBmt¹ and Val⁵). While starting with the CsA/LiCl‐derived conformation, the conversion is facile. It is illustrated that these calculations, which are of artificial character, using only the starting and final structures of the observed conformational transition during the receptor‐binding event, allow an insight into the interactions between the substrates and receptor in terms of an induced fit.